Systematic network pharmacology and KEGG-GO pathway analysis reveal collagen-induced arthritis as the one of the highly pathologically relevant preclinical model for rheumatoid arthritis

Background A chronic, systemic inflammatory illness, rheumatoid arthritis (RA), causes increasing joint inflammation and bone erosion, which leads to disability in systemic complications. The current study is being performed to identify highly pathologically relevant models commonly used for arthritis using network pharmacology. Methods Initially, genes from the literature review (LOR) and GeneCards databases were collected to first identify the genes regulated by RA and five arthritis inducing agents. The STRING server was used for functional enrichment analysis. Cytoscape 3.10.3 was used to build the networks of RA, chemicals, genes, and signaling pathways. GO enrichment analysis and KEGG pathway were performed using the ShinyGO 0.74 database. Results This work is the first to identify five selected arthritis models that closely resemble the pathophysiology of RA. First, the genes that RA and the five models regulate were identified by combining information from GeneCards and LOR. Approximately 201 genes were altered by RA, of which 28.7%, 24.1% and 24.1% of the genes were common for collagen-induced, formaldehyde-induced, and zymosan-induced arthritis. In accordance with the enrichment analysis, NF-κB, IL-17, JAK-STAT, PI3K-Akt, B cell receptor, chemokine, T cell receptor, TNF, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, osteoclast differentiation, Th1 and Th2 cell differentiation, Th17 cell differentiation, and leukocyte transendothelial migration are all signaling pathways that RA activates. In addition, Collagen, Formaldehyde, and Zymosan induced arthritis significantly activated these pathways, with higher gene counts and lower FDR scores. GO functional enrichment analysis revealed significant similarity in biological processes, molecular function, and cellular components shared between the RA and CIA. Conclusion According to this in silico study, collagen-induced arthritis could be a highly pathologically relevant model for arthritis. Network pharmacology provides a systems-level framework for selecting appropriate preclinical models to investigate RA pathophysiology and therapeutic strategies.